title: Glucosamine, a naturally occurring amino monosaccharide modulates LL-37-induced endothelial cell activation.
abstract: Atheroscleros is now considered as a chronic inflammatory disease, and glucosamine has a potential to exhibit anti-inflammatory action. Thus, we investigated the effect of glucosamine on LL-37-induced endothelial cell activation. HUVEC (human umbilical vein endothelial cells) were stimulated by LL-37 in the presence or absence of glucosamine (0.01-1 mM) or its analogue, N-acetylglucosamine (0.1-1 mM). mRNA expression of MCP-1 (monocyte chemoattractant protein-1) and ICAM-1 (intercellular adhesion molecule-1) was evaluated by real-time RT-PCR, and their protein levels were analyzed by ELISA and Western blotting, respectively. Furthermore, the effect of glucosamine on O-N-acetylglucosamine (O-GlcNAc) modification was evaluated by Western blotting. Glucosamine but not N-acetylglucosamine suppressed the LL-37-induced expression of MCP-1 and ICAM-1 at both mRNA (p<0.05 at 0.1 mM) and protein levels (p<0.05 at 1 mM). Of interest, O-GlcNAc modification was induced by incubating HUVEC with glucosamine (p<0.05 at 1 mM) but not N-acetylglucosamine. Of note, alloxan, an O-N-acetylglucosamine transferase inhibitor, which prevented the glucosamine-induced O-GlcNAc modification, abrogated the suppressive effect of glucosamine on MCP-1 and ICAM-1 expression (p<0.05 at 0.5 mM). These observations suggest that glucosamine modulates endothelial cell activation possibly via O-GlcNAc modification, and may exhibit an anti-inflammatory action on atherosclerosis.
authors.affiliation: Department of Host Defense and Biochemical Research, Juntendo University, School of Medicine, Hongo, Tokyo 113-8421, Japan.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Ju
authors.forename: Jian
authors.initials: J
authors.lastname: Hua
authors.forename: Koji
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000378:metabolism* / Q000473:pathology; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018799:Intercellular Adhesion Molecule-1; D000117:Acetylglucosamine; D054804:Cathelicidins